Without limiting the scope of the invention, its background is described in connection with methods and compositions for diagnosis and treatment of lung cancer.
Lung cancer is the leading cause of cancer-related deaths, worldwide. Approximately 226,160 new cases and 160,340 deaths are expected in the Unites States in 2012 (1). The World Health Organization classifies lung cancer into four major histological types: (1) squamous cell carcinoma (SCC), (2) adenocarcinoma, (3) large cell carcinoma, and (4) small cell lung carcinoma (SCLC). The term non-small cell lung carcinoma (NSCLC) includes squamous, adenocarcinoma and large cell carcinomas.
Although the occurrence of breast cancer is slightly more common in the United States, lung cancer is second behind prostate cancer for males and third behind breast and colorectal cancers for women. Yet, lung cancer is the most common cause of cancer deaths. Typically, a combination of X-ray and sputum cytology is used to diagnose lung cancer. Unfortunately, by the time a patient seeks medical help for their symptoms, the cancer is at such an advanced state it is usually incurable.
The majority (85%) of lung cancer cases are of the non-small cell lung cancer (NSCLC) type and the 5-year survival rate for all patients diagnosed with NSCLC is estimated to be less than 20%. Standard treatments for NSCLC include chemotherapy, radiation therapy, surgery or a combination of these treatments. Unfortunately, these therapeutic interventions are associated with significant side effects (2), and generally offer patients limited benefits (3). Despite the recent addition of molecular target therapies to our armamentarium, the more recent addition to the armamentarium against NSCLC are targeted therapies. Unfortunately, despite the therapeutic advantages afforded by these agents such those based on the monoclonal antibodies bevacizumab, they can be used only in 16.5% of chemotherapy recipients (1, 4). NSLC is still is the leading cause of cancer-related deaths in the world. Therefore, there is an urgent need to develop more effective therapies for patients suffering from this devastating disease.
U.S. Pat. No. 5,773,579, entitled, “Lung cancer marker,” discloses an isolated and purified nucleic acid sequence and corresponding amino acid sequence to a novel protein specific for human lung cancer cells. This gene is expressed at a much higher level in these cells than in normal lung cells, other normal tissues and other tumor cell lines tested. Also disclosed are three additional recombinant forms of this gene and protein, in the first two cases a membrane spanning region is removed and in the third case, an amino acid is changed by in vitro mutagenesis.
U.S. Patent Application Publication No. 2012/0100558, entitled, “Lung Cancer Diagnosis,” is directed to the diagnosis of lung cancer in a subject before onset of symptoms in which the method includes screening a biological fluid from the subject for the presence therein of autoantibodies that are specific for one or more pre-diagnostic lung cancer indicator proteins, including LAMR1, and optionally additionally or alternatively including annexin I and/or 14-3-3-theta and/or other pre-diagnostic lung cancer indicator proteins as presently disclosed, as the defined antigens.
U.S. Patent Application Publication No. 2011/0177079, entitled, “Cancer-testis antigens,” discloses cancer-testis antigens and the nucleic acid molecules that encode them. The invention also relates to the use of the nucleic acid molecules, polypeptides and fragments thereof in methods and compositions for the diagnosis and treatment of diseases, such as cancer. More specifically, the invention relates to the discovery of novel cancer-testis (CT) antigens.
U.S. Patent Application Publication No. 2010/0291156, entitled, “Composition for Treating Lung Cancer, Particularly of Non-Small Lung Cancers (NSCLC),” is directed to active (immunostimulatory) compositions with at least one RNA, preferably an mRNA, encoding at least two (preferably different) antigens capable of eliciting an (adaptive) immune response in a mammal. The invention is also said to teach a vaccine comprising said active (immunostimulatory) composition, and to the use of said active (immunostimulatory) composition (for the preparation of a vaccine) and/or of the vaccine for eliciting an (adaptive) immune response for the treatment of lung cancer, particularly of non-small cell lung cancers (NSCLC), preferably selected from the three main sub-types squamous cell lung carcinoma, adenocarcinoma and large cell lung carcinoma, or of disorders related thereto.